Treatment of disorders by unidirectional nerve stimulation

ABSTRACT

Apparatus ( 18 ) for treating a condition of a subject is provided. An electrode device ( 100 ) is adapted to be coupled to longitudinal nervous tissue ( 40 ) of the subject, and a control unit ( 50 ) is adapted to drive the electrode device to apply to the nervous tissue a current which is capable of inducing action potentials that propagate in the nervous tissue in a first direction, so as to treat the condition. The control unit is further adapted to suppress action potentials from propagating in the nervous tissue in a second direction opposite to the first direction.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 09/944,913, filed Aug. 31, 2001, entitled, “Treatment ofdisorders by unidirectional nerve stimulation.” which is assigned to theassignee of the present patent application and is incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates generally to treating patients byapplication of electrical signals to a selected nerve or nerve bundle,and specifically to methods and apparatus for stimulating nerve tissuewhile minimizing possible accompanying side effects.

BACKGROUND OF THE INVENTION

The use of nerve stimulation for treating and controlling a variety ofmedical, psychiatric, and neurological disorders has seen significantgrowth over the last several decades. In particular, stimulation of thevagus nerve (the tenth cranial nerve) has been the subject ofconsiderable research. The vagus nerve is composed of somatic andvisceral afferents (inward conducting nerve fibers, which conveyimpulses toward the brain) and efferents (outward conducting nervefibers, which convey impulses to an effector to regulate activity suchas muscle contraction or glandular secretion). The vagus nerve isresponsible for controlling and/or receiving feedback from variousglands, the pharynx, larynx, heart, lungs, liver, stomach, intestine,and ureters. Because of its large number of functions with respect to arange of body systems, the vagus nerve is preferred in many applicationsfor purposes of modulating the functions of designated organs orportions of the central nervous system (CNS).

U.S. Pat. No. 5,540,730 to Terry et al., which is incorporated herein byreference, describes a method for treating motility disorders byapplying a signal to the vagus nerve of a patient, in order to stimulateor inhibit neural impulses and produce excitatory or inhibitoryneurotransmitter release by the nerve, according to the specific natureof the motility disorder.

U.S. Pat. Nos. 5,188,104 and 5,263,480 to Wernicke et al., which areincorporated herein by reference, describe a method for treatingcompulsive eating disorders by applying a stimulating signal to thevagus nerve of the patient appropriate to alleviate the effect of theeating disorder. For example, in cases where the disorder is compulsiveeating, the stimulating signal is described as being calibrated toproduce a sensation of satiety in the patient. In cases where thedisorder is compulsive refusal to eat (anorexia nervosa), thestimulating signal is described as being calibrated to produce asensation of hunger or to suppress satiety in the patient.

U.S. Pat. No. 5,571,150 to Wernicke et al., which is incorporated hereinby reference, describes a method for treating a comatose patient bystimulating a cranial nerve, preferably the vagus nerve, in order tomodulate the activity of the nerve in an effort to rouse the patientfrom the coma.

U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 to Zabara, which areincorporated herein by reference, generally describe methods forcontrolling or preventing epileptic seizures and other motor disordersby stimulating the vagus nerve.

U.S. Pat. No. 6,205,359 to Boveja, which is incorporated herein byreference, describes apparatus for treating various forms of epilepsyand involuntary movement disorders by electrical stimulation of the leftvagus nerve.

U.S. Pat. No. 5,205,285 to Baker, which is incorporated herein byreference, describes a device designed to avoid undesirable voicemodulation of patients undergoing vagal stimulation therapy, whilemaintaining a bias in certain circumstances toward ongoing delivery ofthe therapy. In essence, this device requires the addition of sensingmeans to detect the patient's attempts at speech, responsive to whichthe device halts or delays the vagal stimulation during the time thatspeech attempts continue to be detected.

U.S. Pat. No. 5,299,569 to Wernicke et al., which is incorporated hereinby reference, describes a method for treating and controllingneuropsychiatric disorders, including schizophrenia, depression andborderline personality disorder, by selectively applying a predeterminedelectrical signal to the patient's vagus nerve, in order to alleviatethe symptoms of the disorder being treated.

U.S. Pat. No. 5,335,657 to Terry et al., which is incorporated herein byreference, describes a method for treating and controlling sleepdisorders by applying an electrical signal to the vagus nerve in orderto modulate electrical activity of afferent fibers of the nerve.

U.S. Pat. No. 5,707,400 to Terry et al., which is incorporated herein byreference, describes a method for treating patients suffering fromrefractory hypertension, also by stimulating the vagus nerve.

As is seen from this list of patents, stimulation of the nervous system,particularly the vagus nerve, for therapeutic purposes has been thesubject of a considerable amount of research and application to medical,psychiatric, and neurological disorders. However, other than the problemof speech impairment addressed by the above-cited U.S. Pat. No.5,205,285 to Baker, the possible unwanted side effects, both proven andpotential, of selective stimulation of the vagus nerve, have not beengiven extensive consideration.

U.S. Pat. No. 5,282,468 to Klepinski, which is incorporated herein byreference, describes an implantable neural electrode.

U.S. Pat. No. 4,628,942 to Sweeney et al., which is incorporated hereinby reference, describes an asymmetric, shielded, two-electrode cuff forstimulating a nerve.

U.S. Pat. No. 4,535,785 to van den Honert et al., describes implantableelectronic apparatus.

U.S. Pat. No. 4,602,624 to Naples et al., which is incorporated hereinby reference, describes an implantable electrode cuff for applyingsignals to nerves.

U.S. Pat. No. 5,199,430 to Fang et al., which is incorporated herein byreference, describes implantable electronic apparatus for assisting theurinary sphincter to relax.

U.S. Pat. No. 5,215,086 to Terry et al., which is incorporated herein byreference, describes a method for applying electrical stimulation totreat migraine headaches.

U.S. Pat. No. 5,755,750 to Petruska et al., which is incorporated hereinby reference, describes a method for selectively inhibiting activity innerve fibers.

U.S. Pat. Nos. 4,649,936 to Ungar et al., and 4,608,985 to Chrish etal., which are incorporated herein by reference, describe apparatus andmethods for selectively blocking action potentials passing along a nervetrunk.

PCT Patent Publication WO 01/10375 A2 to Felsen et al., which isincorporated herein by reference, describes a method for inhibitingaction potential generation in nervous tissue.

The following articles may be of interest, and are incorporated hereinby reference:

“Generation of unidirectionally propagating action potentials using amonopolar electrode cuff,” Annals of Biomedical Engineering, vol. 14,pp. 437-450, 1986 by Ira J. Ungar et al.

“An asymmetric two electrode cuff for generation of unidirectionallypropagated action potentials,” IEEE Transactions on BiomedicalEngineering, vol. BME-33, No. 6, June 1986 by James D. Sweeney et al.

“A spiral nerve cuff electrode for peripheral nerve stimulation,” byGregory G. Naples et al., IEEE Transactions on Biomedical Engineering,vol. 35, No. 11, November 1988.

“A nerve cuff technique for selective excitation of peripheral nervetrunk regions,” by James D. Sweeney et al., IEEE Transactions onBiomedical Engineering, vol. 37, No. 7, July 1990.

“Generation of unidirectionally propagated action potentials in aperipheral nerve by brief stimuli,” Science, vol. 206, pp. 1311-1312,December 1979.

“Generation of unidirectionally propagated action potentials in aperipheral nerve by brief stimuli,” van den Honert et al., 206 Science1311-1312, (Dec. 14, 1979).

“A technique for collision block of peripheral nerve: Frequencydependence,” van den Honert, C., Mortimer, J. T.: MP-12, IEEE Trans.Biomed. Eng. 28:379-382, 1981.

“A technique for collision block of peripheral nerve: Single stimulusanalysis,” van den Honert, C., Mortimer, J. T.: MP-11, IEEE Trans.Biomed. Eng. 28:373-378, 1981.

“A Nerve Cuff Design for the Selective Activation and Blocking ofMyelinated Nerve Fibers,” D. M. Fitzpatrick et al., Ann. Conf. of theIEEE Eng. in Medicine and Biology Soc., Vol. 13, No. 2, pp. 906, 1991.

“Acute Animal Studies on the Use of Anodal Block to Reduce UrethralResistance in Sacral Root Stimulation,” N. J. M. Rijkhof et al., IEEETransactions on Rehabilitation Engineering, Vol. 2, No. 2, pp. 92, 1994.

“Orderly Recruitment of Motoneurons in an Acute Rabbit Model,” N. J. M.Rijkhoff et al., Ann. Conf. of the IEEE Eng., Medicine and Biology Soc.,Vol. 20, No. 5, pp. 2564, 1998.

“Orderly Stimulation of Skeletal Muscle Motor Units with Tripolar NerveCuff Electrode,” R. Bratta et al., IEEE Transactions on BiomedicalEngineering, Vol. 36, No. 8, pp. 836, 1989.

U.S. Pat. No. 5,423,872 to Cigaina, which is incorporated herein byreference, describes a method for pacing the stomach in order to alterits natural rhythm. The principle espoused in Cigaina is that byaltering the rhythm, one can either delay or speed up gastric emptying.Cigaina indicates that many different disorders, includinggastroesophageal reflux disorder (GERD), can be treated using the rhythmaltering method.

U.S. Pat. No. 5,716,385 to Mittal et al., which is incorporated hereinby reference, describes a system to treat GERD by stimulating theskeletal muscle tissue of the crural diaphragm whenever myoelectricmeasurements made on the diaphragm are indicative of relaxation thereof.Stimulation of the diaphragm is intended to indirectly cause contractionof the lower esophageal sphincter (LES), and thereby inhibit a refluxevent which is assumed to accompany relaxation of the diaphragm.

U.S. Pat. No. 6,097,984 to Douglas, which is incorporated herein byreference, discloses a system to treat GERD by continually simulatingthe LES of a patient in order to maintain it in a closed state, therebypreventing reflux. Stimulation is removed only when swallowing isdetected, to allow food pass into the stomach.

U.S. Pat. Nos. 6,104,955, 6,091,992, and 5,836,994 to Bourgeois,6,026,326 to Bardy, 6,083,249 to Familoni, 5,690,691 to Chen, 5,292,344to Douglas, and 3,411,507 to Wingrove, which are incorporated herein byreference, describe methods and apparatus for electrical simulation ofthe GI tract to treat various physiological disorders.

U.S. Pat. Nos. 4,585,005 to Lue et al., 4,663,102 to Brenman et al.,5,439,938 to Snyder et al., 5,454,840 to Krakovsky et al., 5,938,584 toArdito et al., and 6,169,924 to Meloy et al., which are incorporatedherein by reference, describe systems for applying electricalstimulation to treat erectile dysfunction.

U.S. Pat. No. 4,338,945 to Kosugi et al., which is incorporated hereinby reference, describes a randomized electrical stimulation system forproviding pain relief. In particular, the Kosugi patent describes asystem for generating electrical pulses for relieving a patient's painthat includes a pulse generator and a controller for modulating theparameters of the output pulses of the pulse generator to fluctuate inaccordance with a 1/f rule, i.e., such that the spectral density of thefluctuation varies inversely with the frequency. It is noted in thatpatent that conventional stimulation pulse trains have “. . .stimulation parameters such as pulse rate, pulse width and pulseamplitude [which] do not change in time course. After a long-time use ofsuch a stimulation which adopts uniform or simple periodic stimuli, thenervous system reveals adaptation effect against the stimuli.”

SUMMARY OF THE INVENTION

It is an object of some aspects of the present invention to provideapparatus and methods for treating and controlling a medical conditionby application of electrical signals to a selected nerve or nervebundle.

It is also an object of some aspects of the present invention to provideapparatus and methods for treating and controlling a medical conditionby application of electrical signals to a selected nerve or nerve bundlewhile minimizing adverse side effects.

It is a further object of some aspects of the present invention toprovide apparatus and methods for treatment of sleep disorders whileminimizing adverse side effects.

It is still a further object of some aspects of the present invention toprovide apparatus and methods for treatment of neuropsychiatricdisorders while minimizing adverse side effects.

It is yet a further object of some aspects of the present invention toprovide apparatus and methods for treatment of eating disorders, whileminimizing adverse side effects caused by stimulation of the nervescontrolling the digestive system.

It is an additional object of some aspects of the present invention toprovide apparatus and methods for treatment of motility disorders, whileminimizing undesired side effects caused by stimulation of the nervescontrolling the digestive system.

It is yet an additional object of some aspects of the present inventionto provide apparatus and methods for rousing comatose patients, whileminimizing adverse effects upon physiological functions.

It is still an additional object of some aspects of the presentinvention to provide apparatus and methods for treating epilepsy andinvoluntary movement disorders while minimizing unwanted side effectssuch as impairment of speech.

It is also an object of some aspects of the present invention to provideapparatus and methods for treating hypertension while minimizingunwanted side effects.

It is a further object of some aspects of the present invention toprovide improved methods and apparatus for treating erectile dysfunctionor other sexual disorders in males and females.

It is still a further object of some aspects of the present invention toprovide improved methods and apparatus for treating congestive heartfailure, arrhythmia, and other cardiac pathologies.

It is yet a further object of some aspects of the present invention toprovide improved methods and apparatus for treating pulmonarypathologies such as chronic obstructive pulmonary disease (COPD).

It is also an object of some aspects of the present invention to provideimproved methods and apparatus for treating hyperhidrosis.

In preferred embodiments of the present invention, apparatus fortreating a specific condition comprises a set of one or more electrodedevices that are applied to one or more selected sites of the central orperipheral nervous system of a patient. A control unit preferably drivesthe electrode devices to: (a) apply signals which induce the propagationof nerve impulses in a desired direction in order to treat thecondition, and (b) suppress artificially-induced nerve impulses in theopposite direction in order to minimize adverse side effects of thesignal application.

For some applications of the present invention, the signal is applied toa nerve such as the vagus nerve, in order to stimulate efferent fibersand increase the motor activity of the small intestine and colon, andthereby treat motility disorders. Simultaneously, action potentialpropagation is inhibited in afferent fibers responsive to theapplication of the signals. In the prior art, such as that described inthe above-cited U.S. Pat. No. 5,540,730 to Terry et al., the vagus nerveis stimulated so as to influence the motor activity of the smallintestine and colon. However, an unintended result of applying themethod of the Terry patent is that, when the nerve is stimulated, actionpotentials are induced in both directions (stimulating afferent andefferent fibers). Stimulation of the vagus nerve as a whole may thusproduce undesired afferent stimulation, which may in turn result in, forexample, the initiation of undesired or counterproductive feedback tothe brain, and resultant undesired sensations or activity of thedigestive system (e.g., nausea). Advantageously, and unlike the priorart, application of these embodiments of the present inventionsubstantially stimulates only the intended efferent fibers, and reducesor eliminates the transmission of sensory signals to the CNS that couldcause such undesirable responses in the digestive system.

For some applications of the present invention, the signal is applied toa portion of the vagus nerve innervating the stomach in order tostimulate sensory fibers and thereby produce a sensation, e.g., satietyor hunger. In the prior art, such as that described in the above-citedU.S. Pat. No. 5,263,480 to Wernicke et al., the vagus nerve isstimulated so as to induce certain sensory messages to propagate to thebrain. However, upon the application of stimulation as described byWernicke, action potentials are induced in both directions—on afferentand efferent fibers—and may thus generate unwanted effector responses.Depending upon the location on the vagus nerve at which stimulation isapplied, such impulses may, for example, stimulate the glands of thestomach to secrete excessive hydrochloric acid, or they may reduce orotherwise affect the heartbeat of the patient. Unlike the prior art,application of this embodiment of the present invention generatessubstantially only sensory signals, and generally does not causeefferent signals to be transmitted to the effectors that could result insuch undesirable responses.

For some applications, the signal is applied to the vagus nerve so as tomodulate electrical activity in the brain, and thereby rouse a patientfrom a comatose condition. At the same time, the electrode devices aredriven to inhibit action potentials in efferent fibers which wouldgenerally arise as a result of the application of the signal. In theprior art, such as that described in U.S. Pat. No. 5,571,150 to Wernickeet al., the vagus nerve in the neck is stimulated so as to causeafferent nerve fibers to conduct modified electrical patterns toward thereticular formation. However, inadvertent stimulation of efferent fibersresulting from the bi-directional nature of artificial nerve stimulationmay result in undesirable motor, glandular or cardiac activity. Unlikethe prior art, this application of the present invention inhibits actionpotentials in the efferent fibers, and consequently generally does notcause unwanted efferents to be generated.

Alternatively, the signal is applied to the vagus nerve to treatepilepsy and involuntary movement disorders, while action potentialpropagation responsive to the signal in efferent fibers is suppressed.In the prior art, either the left or right vagus nerve is stimulated asdescribed in the above-cited Zabara and Boveja patents. The basicpremise of vagal nerve stimulation for control of epileptic seizures isthat vagal afferents have a diffuse central nervous system (CNS)projection, and activation of these pathways has a widespread effect onneuronal excitability. However, the mechanism by which vagal stimulationexerts its influence on seizures is not well understood.

The inventors of the present invention believe that the techniquesdescribed in the Zabara and Boveja patents induce unintended and, atleast to some extent, undesirable accompanying effects resulting fromthe stimulation of efferent fibers at the same time as the treatment isbeing applied. It is well known, for example, that stimulation of theright vagus can lead to profound bradycardia (slowing of the heartbeat),which is an unwanted and unnecessary complication. Additionally, it hasbeen determined that a side effect of vagal stimulation in epilepticpatients is the presence of a noticeable modulation or reduction of thepatient's voice when he or she tries to speak during application of thestimulating signals to the nerve. U.S. Pat. No. 5,205,285 to Baker,cited above, addresses the problem of voice modulation, but requires theaddition of a sensor to detect the patient's speech and simplyterminates the vagal stimulation, i.e., the desired treatment, wheneverspeech attempts continue to be detected. A drawback of this solution isthat beneficial therapy may be unduly inhibited in favor of cosmetic orsecondary considerations. Unlike the limitations of the prior art,however, application of this embodiment of the present inventionsubstantially precludes the onset of these accompanying effects bypermitting nerve impulses to travel only in the desired direction.

For some applications of the present invention, the signal is applied tothe vagus nerve in order to treat and control sleep disorders orhypertension, while inhibiting action potential propagation in efferentfibers responsive to the applied signal. In the prior art, such as thatdescribed in U.S. Pat. Nos. 5,335,657 and 5,707,400 to Terry et al.,bi-directional impulses are generated by the stimulation, resulting inboth the desired treatment as well as unintended and not necessarilybeneficial accompanying physiological responses. Unlike the prior art,however, application of this embodiment of the present inventionsubstantially does not stimulate electrical activity of efferent fibersthat may generate unwanted visceral, glandular, or motor responses.

In a preferred embodiment, the signal is applied to the pelvic nerve, oranother nerve, in order to treat erectile dysfunction. Preferably, thesignal is configured so as to cause the arterial dilation responsiblefor erection, and is applied in a stimulatory mode to parasympatheticfibers, and/or in an inhibitory mode to sympathetic fibers.Alternatively or additionally, in order to support ejaculationpreferably following a period of erection, the signal is applied in aninhibitory mode to parasympathetic fibers, and/or in a stimulatory modeto sympathetic fibers. For some applications, the signal is applied in aunidirectional mode, so as to prevent undesired action potentials frombeing conveyed to the brain in response to the applied signal. For otherapplications, the signal is applied in a unidirectional mode, so as toprevent undesired action potentials from being conveyed to the penis inresponse to the applied signal.

For some embodiments in which it is desired to assist a patient infacilitating or maintaining an erection, signal application modes areutilized to block or reduce action potentials in sympathetic nervefibers such as sympathetic C fibers that would otherwise: (a) beconveyed to the penis, (b) cause the constriction of arteries thereof,and, consequently, (c) inhibit an erection. By blocking these actionpotentials, the inhibition to erection is removed, and the erection canoccur. Preferably, in order to facilitate erection, a series of pulsesare applied to a site on the pelvic nerve or another nerve, so as togenerate action potentials which travel in a central direction (i.e.,towards the brain or spinal cord), and then collide withperipherally-directed, erection-inhibiting natural action potentials andterminate the propagation of these natural action potentials.Simultaneously, anodal blocking or another technique is used to preventthe applied pulses from inducing new peripherally-directed actionpotentials along the same fibers, which in the absence of the anodalblock would inhibit an erection.

It is to be understood that whereas these embodiments of the presentinvention are described with respect to enhancing sexual functioning ina male, the same principles may be adapted for use in enhancing sexualfunctioning in a female, mutatis mutandis, e.g., so as to facilitate theengorgement of vulval erectile tissue with blood, or to relievevaginismus. It is similarly to be understood that whereas thesetreatments for erectile dysfunction are described with respect to signalapplication to the pelvic nerve, this is by way of illustration and notlimitation, and the scope of the present invention includes theapplication of electrical waveforms to other nerves, such as thecavernous nerve, the pudendal nerve, or to sacral nerve roots.

In summary, the stimulation of nerve impulses in one direction whilesuppressing impulses in the opposite direction is preferably used toobtain the benefits of various new or prior art therapeutic treatments,including, but not limited to, those described in the references citedherein, while reducing or eliminating adverse and/or unintended sideeffects.

There is therefore provided, in accordance with a preferred embodimentof the present invention, a method for treating a condition of asubject, including:

driving into longitudinal nervous tissue of the subject a current whichis capable of inducing action potentials that propagate in the nervoustissue in a first direction, so as to treat the condition; and

suppressing action potentials from propagating in the nervous tissue ina second direction opposite to the first direction.

For some applications, driving the current includes driving a currentcapable of inducing action potentials that propagate in the nervoustissue in an afferent direction with respect to the central nervoussystem of the subject. For other applications, driving the currentincludes driving a current capable of inducing action potentials thatpropagate in the nervous tissue in an efferent direction with respect tothe central nervous system of the subject.

In various preferred embodiments, driving the current includes drivingthe current into one or more of the following: a vagus nerve of thesubject, a pelvic nerve of the subject, a pudendal nerve of the subject,a cavernous nerve of the subject, a spinal nerve root of the subject, acervical nerve of the subject, a sympathetic nerve of the subject, aparasympathetic nerve of the subject, nervous tissue of the centralnervous system of the subject, nervous tissue of the peripheral nervoussystem of the subject, a nerve of the subject that provides sympatheticinnervation to a heart of the subject, a nerve of the subject thatprovides parasympathetic innervation to a heart of the subject, a nerveof the subject that provides sympathetic innervation to a lung of thesubject, a nerve of the subject that provides parasympatheticinnervation to a lung of the subject, and a nerve that modulateshidrosis of the subject.

Preferably, driving the current includes selecting at least oneparameter of the current in accordance with a stochastic process.

For some applications, the method includes driving the current andsuppressing the action potentials at substantially the same time.

In a preferred embodiment, suppressing the action potentials includesregulating the suppressing of the action potentials so as to inhibit anundesired response of the central nervous system of the subjectgenerated responsive to driving the current into the nervous tissue.

In a preferred embodiment, suppressing the action potentials includesregulating the suppressing of the action potentials so as to inhibit anundesired sensation generated responsive to driving the current into thenervous tissue.

Typically, but not necessarily, suppressing the action potentialsincludes suppressing action potentials induced responsive to driving thecurrent.

As appropriate, driving the current may include configuring the currentto be capable of treating one or more of the following: a sleep disorderof the subject, an involuntary movement disorder of the subject, agastrointestinal motility disorder of the subject, an eating disorder ofthe subject, obesity of the subject, anorexia of the subject, agastrointestinal tract disorder of the subject, hypertension of thesubject, muscle spasm of the subject, vaginismus of the subject, coma ofthe subject, an aspect of heart failure of the subject, an aspect ofcardiac arrhythmia of the subject, tachycardia of the subject,bradycardia of the subject, or an aspect of chronic obstructivepulmonary disorder (COPD) of the subject.

In a preferred embodiment, the method includes implanting electrodes ina vicinity of the nervous tissue, wherein driving the current includesdriving the current through the electrodes on a chronic basis. Inanother preferred embodiment, the method includes placing electrodes ina vicinity of the nervous tissue in response to an acute occurrence,wherein driving the current includes driving the current through theelectrodes, and wherein the method includes removing the electrodesfollowing the acute occurrence.

In a preferred application, driving the current includes configuring thecurrent to be capable of treating epilepsy of the subject. For example,driving the current may include driving the current into a vagus nerveof the subject, and configuring the current to be capable of treatingepilepsy of the subject. In this case, suppressing the action potentialsmay include suppressing action potentials that interfere with an abilityof the subject to speak.

In a preferred embodiment, driving the current includes applying to avagus nerve of the subject a current capable of inducing constriction ofa lower esophageal sphincter of the subject.

For some applications, suppressing the action potentials includessuppressing the action potentials repeatedly, during a series oftemporally non-contiguous action potential suppression periods. In thiscase, the method preferably includes substantially withholding thesuppressing of action potentials between the action potentialsuppression periods.

In a preferred embodiment, the method includes sensing an indication ofa presence of the condition, wherein driving the current includesdriving the current responsive to sensing the indication. For example,the method may include receiving an input from the subject, whereindriving the current includes driving the current responsive to receivingthe input.

As appropriate, driving the current may include configuring the currentso as to induce action potential propagation primarily in A fibers ofthe nervous tissue, primarily in B fibers of the nervous tissue, and/orprimarily in C fibers of the nervous tissue.

For some applications, driving the current includes configuring thecurrent to be such as to induce action potentials that travel in thefirst direction in the nervous tissue and collide with and inhibitnatural action potentials propagating in the second direction in thenervous tissue. In this case, the step of suppressing action potentialspreferably includes suppressing propagation of action potentials thatare generated as a result of the step of driving the current into thenervous tissue.

In a preferred embodiment, suppressing the action potentials includesidentifying an action potential conduction velocity and suppressingaction potentials characterized by the identified conduction velocity.Typically, the method includes withholding suppression of an actionpotential having a conduction velocity substantially different from theidentified conduction velocity.

In a preferred embodiment, suppressing the action potentials includesregulating the suppressing of the action potentials so as to inhibit anundesired effector action responsive to driving the current into thenervous tissue. For example, suppressing the action potentials mayinclude suppressing generation of action potentials that induceincreased acid secretion in a gastrointestinal tract of the subject,suppressing generation of action potentials that induce muscularcontraction, or suppressing generation of action potentials that inducebradycardia.

For some applications, driving the current includes configuring thecurrent to be capable of treating pain of the subject. In this case (orin the treatment of any of the conditions described herein), driving thecurrent includes applying pulses having pulse durations greater than 0.1milliseconds. Alternatively or additionally, driving the currentincludes applying pulses having pulse durations less than 2milliseconds. Further alternatively or additionally, driving the currentincludes applying pulses having a frequency less than 50 Hz. For someapplications, driving the current includes applying pulses at at leasttwo sites on the nervous tissue, and setting a frequency of pulseapplication at each site to be less than 30 Hz. Moreover, in accordancewith a preferred embodiment of the present invention, driving thecurrent includes applying pulses at at least three sites on the nervoustissue, and setting a frequency of pulse application at each site to beless than 20 Hz. In this case, driving the current may include applyingpulses at at least three sites on the nervous tissue, and setting afrequency of pulse application at each site to be less than 10 Hz. Forthese applications, the method may include designating an inter-sitespacing separating each of the at least three sites to be at least 1centimeter, or at least 3 centimeters.

Preferably, driving the current includes driving a first current betweena cathode and a first anode, which are electrically coupled torespective first and second longitudinal sites of the nervous tissue,wherein suppressing the action potentials includes driving a secondcurrent through the cathode and a second anode, which second anode iselectrically coupled to a third site of the nervous tissue, and whereinthe first site is disposed between the second and third sites. In thiscase, driving the first and second currents includes configuring thesecond current to be at least 1.5 times greater than the first current.For some applications, driving the first and second currents includesconfiguring the second current to be at least 3 times greater than thefirst current.

In accordance with a preferred embodiment of the present invention,driving the current includes driving the current into a nerve of thesubject that modulates an aspect of sexual functioning of the subject.For example, driving the current may include configuring the current soas to facilitate engorgement of erectile tissue of the subject.Alternatively or additionally, driving the current includes configuringthe current so as to facilitate an orgasmic response by the subject.

For some applications, driving the current includes:

configuring the current in a first mode so as to facilitate engorgementof erectile tissue of the subject; and

configuring the current in a second mode, different from the first mode,so as to facilitate an orgasmic response by the subject.

As appropriate, driving the current may include driving the current intoa nerve of a male subject or into a nerve of a female subject.Similarly, driving the current may include driving the current into aparasympathetic nerve of the subject or into a sympathetic nerve of thesubject, depending on the desired response.

For some applications, driving the current includes configuring thedriving of the current such that the first direction includes adirection along the nerve away from a central nervous system (CNS) ofthe subject.

In this case, driving the current may include:

driving the current into a parasympathetic nerve of the subject; and

configuring the current to be such as to induce action potentials thatfacilitate engorgement of erectile tissue of the subject.

Alternatively or additionally, driving the current may include:

driving the current into a sympathetic nerve of the subject; and

configuring the current to be such as to induce action potentials thatfacilitate an orgasmic response by the subject.

For some applications, driving the current includes configuring thedriving of the current such that the first direction includes adirection along the nerve towards a central nervous system (CNS) of thesubject.

In this case, driving the current may include:

driving the current into a sympathetic nerve of the subject; and

configuring the current to be such as to induce action potentials thattravel towards the CNS and collide with and inhibit natural actionpotentials propagating away from the CNS, which natural actionpotentials would otherwise inhibit engorgement of erectile tissue of thesubject.

Alternatively or additionally, driving the current may include:

driving the current into a parasympathetic nerve of the subject; and

configuring the current to be such as to induce action potentials thattravel towards the CNS and collide with and inhibit natural actionpotentials propagating away from the CNS, which natural actionpotentials would otherwise inhibit an orgasmic response by the subject.

Typically, suppressing the action potentials includes applying anelectric field to the nervous tissue. Preferably, applying the fieldincludes applying a plurality of electric fields to the nervous tissueat respective longitudinal sites thereof, e.g., at two adjacent sitesseparated by at least about 2 mm, or at two adjacent sites separated byless than about 4 mm. Applying the plurality of electric fields to thenervous tissue preferably includes applying each of the fields at adifferent respective time. For some applications, applying each of thefields at a different respective time includes applying the fields insequence, in a progression through the respective longitudinal sites ofthe nervous tissue. For example, applying the fields in sequence mayinclude designating a difference between respective times of applicationof the fields at two adjacent ones of the sites to be at least 0.1milliseconds. Moreover, applying the fields in sequence may includedesignating a difference between respective times of application of thefields at two adjacent ones of the sites to be at least 1 millisecond.

There is further provided, in accordance with a preferred embodiment ofthe present invention, a method for treating a subject, including:

driving into a sympathetic nerve of the subject a current having acharacteristic frequency between about 10 and 50 Hz and an amplitudebetween about 0.1 and 20 mA; and

configuring the driving of the current to be such as to inhibit actionpotential propagation in the nerve.

There is still further provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a conditionof a subject, including:

an electrode device, adapted to be coupled to longitudinal nervoustissue of the subject; and

a control unit, adapted to drive the electrode device to apply to thenervous tissue a current which is capable of inducing action potentialsthat propagate in the nervous tissue in a first direction, so as totreat the condition, and adapted to suppress action potentials frompropagating in the nervous tissue in a second direction opposite to thefirst direction.

In a preferred embodiment, the electrode device includes a tripolarelectrode assembly.

Preferably, the tripolar electrode assembly includes a cathode, a firstanode, and a second anode. Further preferably, the cathode is disposedbetween the first and second anodes. Still further preferably, thecathode and the first and second anodes are adapted to be disposed atrespective longitudinal sites of the nervous tissue.

There is yet further provided, in accordance with a preferred embodimentof the present invention, apparatus for treating a subject, including:

an electrode device, adapted to apply current to a sympathetic nerve ofthe subject; and

a control unit, adapted to: (a) drive the electrode device to apply tothe nerve a current having a characteristic frequency between about 10and 50 Hz and an amplitude between about 0.1 and 20 mA, and (b)configure the application of the current to be such as to inhibit actionpotential propagation in the nerve.

The present invention will be more fully understood from the followingdetailed description of the preferred embodiment thereof, taken togetherwith the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a nerve, showing the placement ofelectrode devices thereon, in accordance with a preferred embodiment ofthe present invention;

FIG. 2 is a schematic illustration of a nerve and experimental apparatusapplied thereto, in accordance with a preferred embodiment of thepresent invention; and

FIGS. 3A, 3B, and 3C are graphs showing data measured using theexperimental apparatus of FIG. 2.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 is a schematic illustration of nerve stimulation apparatus 18,for applying electrical energy to induce propagation of impulses in onedirection in a nerve 40, in order to treat a condition, whilesuppressing action potential propagation in the other direction, inaccordance with a preferred embodiment of the present invention. Forillustrative purposes, nerve 40 may be a cranial nerve, such as thevagus nerve, which emanates from the nervous tissue of the centralnervous system (CNS) 30 and transmits sensory signals to CNS 30 andmotor or other effector signals to tissue 20. Apparatus 18 typicallycomprises an implantable or external control unit 50, which drives oneor more electrode devices 100 to apply an appropriate signal torespective sites on nerve 40. It is to be understood that whereaspreferred embodiments of the present invention are described herein withrespect to controlling propagation in a nerve, the scope of the presentinvention includes applying signals to other nervous tissue, such asindividual axons or nerve tracts.

Preferably, control unit 50 receives and analyzes signals from sensors60 located at selected sites in, on, or near the body of the patient.These sensor signals are typically qualitative and/or quantitativemeasurements of a medical, psychiatric and/or neurologicalcharacteristic of a disorder being treated. For example, sensors 60 maycomprise electroencephalographic (EEG) apparatus to detect the onset ofa seizure, or a user input unit, adapted to receive an indication of alevel of discomfort, hunger, or fatigue experienced by the patient.Preferably, the sensor signals are analyzed within control unit 50,which, responsive to the analysis, drives electrode devices 100 to applycurrent to one or more sites on nerve 40, configured such thatapplication thereof stimulates unidirectional propagation of nerveimpulses to treat the specific disorder of the patient.

Alternatively, nerve stimulation apparatus 18 operates without sensors60. In such a preferred embodiment, control unit 50 is typicallypreprogrammed to operate continuously, in accordance with a schedule, orunder regulation by an external source.

For some applications of the present invention, the signals applied bycontrol unit 50 to electrode devices 100 are configured to induceefferent nerve impulses (i.e., action potentials propagating in thedirection of tissue 20), while suppressing nerve impulses traveling innerve 40 towards CNS 30. For illustrative purposes, tissue 20 maycomprise muscle tissue of the gastrointestinal tract, and treatment ofmotility disorders may be accomplished by inducing propagation of nerveimpulses towards the muscle tissue, while suppressing the propagation ofnerve impulses to CNS 30. Preferably, methods and apparatus described inU.S. Pat. No. 5,540,730 to Terry et al. are adapted for use with thisembodiment of the present invention. In contrast to the outcome ofapplication of the apparatus described in the Terry patent, however, inthis embodiment of the present invention, CNS 30 substantially does notreceive sensory signals that could potentially generate undesiredresponses.

Alternatively or additionally, gastroesophageal reflux disease (GERD) istreated by stimulating the vagus nerve unidirectionally, in order toinduce constriction of the lower esophageal sphincter. Advantageously,such an application of unidirectional stimulation inhibits orsubstantially eliminates undesired sensations or other feedback to thecentral nervous system which would in some cases be induced responsiveto stimulation of the vagus nerve. It is noted that this suppression ofafferent impulses is typically only applied during the relatively shorttime periods during which pulses are applied to the vagus nerve, suchthat normal, physiological afferent impulses are in general able totravel, uninhibited, towards the CNS. For some applications, apparatusand methods described in the above-cited U.S. Pat. Nos. 5,188,104,5,716,385 or 5,423,872 are adapted for use with unidirectionalstimulation as provided by this embodiment of the present invention.

For some applications of the present invention, electrode devices 100are configured to induce afferent impulses (i.e., action potentialspropagating in the direction of CNS 30), while suppressing impulses inthe direction of tissue 20. Typically, conditions such as eatingdisorders, coma, epilepsy, motor disorders, sleep disorders,hypertension, and neuropsychiatric disorders are treated by adaptingtechniques described in one or more of the above-cited references foruse with therapeutic unidirectional impulse generation as provided bythese embodiments of the present invention. Advantageously, this avoidsunwanted and not necessarily beneficial outcomes of the prior arttechnique, such as bradycardia, enhanced gastric acid secretion, orother effects secondary to stimulation of the vagus nerve andcommunication of unintended nerve impulses to tissue 20. Which specifictissue 20 receives the efferent stimulation unintentionally induced bythe prior art techniques depends upon the location on the nerve at whichthe stimulation is applied. For example, branchial motor efferents ofthe vagus nerve supply the voluntary muscles of the pharynx and most ofthe larynx, as well as one muscle of the tongue. The visceral efferentsinclude parasympathetic innervation of the smooth muscle and glands ofthe pharynx, larynx, and viscera of the thorax and abdomen.Consequently, unintended efferent signal generation may induce undesiredor unexpected responses in any of the tissue controlled and regulated bythe vagus nerve. In preferred embodiments of the present invention, bycontrast, such responses are suppressed while, at the same time, thedesired afferent nerve signals are transmitted to CNS 30.

A variety of methods for inducing unidirectional propagation of actionpotentials are known in the art, some of which are described in thereferences cited in the Background section of the present patentapplication and may be adapted for use with preferred embodiments of thepresent invention.

In a preferred embodiment, unidirectional signal propagation is inducedusing methods and apparatus disclosed in:

-   -   U.S. Provisional Patent Application 60/263,834 to Cohen and        Ayal, filed Jan. 25, 2001, entitled “Selective blocking of nerve        fibers,” which is assigned to the assignee of the present patent        application and is incorporated herein by reference,    -   U.S. patent application Ser. No. 09/824,682, filed Apr. 4, 2001,        entitled “Method and apparatus for selective control of nerve        fibers,” to Cohen and Ayal, which is assigned to the assignee of        the present patent application and is incorporated herein by        reference,    -   A PCT application, filed on even date with the present patent        application, entitled “Method and apparatus for selective        control of nerve fibers,” to Cohen and Ayal, which is assigned        to the assignee of the present patent application and is        incorporated herein by reference, and/or    -   the above-cited U.S. Pat. Nos. 5,199,430, 4,628,942, and/or        4,649,936.

The Cohen and Ayal regular patent application describes a method for:

(a) selectively suppressing the propagation of naturally-generatedaction potentials which propagate in a predetermined direction at afirst conduction velocity through a first group of nerve fibers in anerve bundle, while

(b) avoiding unduly suppressing the propagation of naturally-generatedaction potentials propagated in the predetermined direction at adifferent conduction velocity through a second group of nerve fibers inthe nerve bundle.

The method includes applying a plurality of electrode devices to thenerve bundle, spaced at intervals along the bundle. Each electrodedevice is capable of inducing, when actuated, unidirectional“electrode-generated” action potentials, which produce collision blockswith respect to the naturally-generated action potentials propagatedthrough the second group of nerve fibers. Moreover, each electrodedevice is actuated in sequence, with inter-device delays timed togenerally match the first conduction velocity and to thereby produce awave of anodal blocks, which: (a) minimize undesired blocking of thenaturally-generated action potentials propagated through the first groupof nerve fibers, while (b) maximizing the generation rate of theunidirectional electrode-generated action potentials which producecollision blocks of the naturally-generated action potentials propagatedthrough the second group of nerve fibers. Such a method may be used forproducing collision blocks in sensory nerve fibers in order to suppresspain, and also in motor nerve fibers to suppress selected muscular orglandular activities.

Alternatively or additionally, embodiments of the present inventioninduce the propagation of unidirectional action potentials usingtechniques described in the above-cited U.S. Pat. Nos. 4,649,936 toUngar et al., and 4,608,985 to Chrish et al., which describe apparatusand methods for selectively blocking action potentials passing along anerve trunk. In this case, electrode device 100 comprises an asymmetric,single electrode cuff, which includes an electrically non-conductive ordielectric sleeve that defines an axial passage therethrough. Thedielectric sheath and axial passage extend from a first end, which isdisposed toward the origin of orthodromic pulses, to a second end. Thegap between the nerve and the cuff is filled by conductive body tissuesand fluids after implantation in the body. A single annular electrode isdisposed in the axial passage, which may be mounted on the inner surfaceof the dielectric sleeve within the axial passage. Other implementationdetails may be found in the Ungar and Chrish patents.

It is to be understood that whereas preferred embodiments of the presentinvention are generally described hereinabove with respect tostimulating and inhibiting action potential propagation in the vagusnerve, the scope of the present invention includes applying analogoustechniques to other central or peripheral nervous tissue of a patient.

Reference is now made to FIGS. 2, 3A, 3B, and 3C. FIG. 2 is a schematicillustration of experimental apparatus which was applied to a ratsciatic nerve 150, in order to block the propagation of actionpotentials in A fibers thereof, in accordance with a preferredembodiment of the present invention. FIGS. 3A, 3B, and 3C are graphsshowing experimental results attained during the use of the apparatus ofFIG. 2, in accordance with a preferred embodiment of the presentinvention.

Bipolar hook electrodes 130 coupled to a stimulus isolator were placedin contact with nerve 150, and were driven to apply a 20 microsecond, 2mA square pulse to the nerve. In this experimental preparation, theseparameters were found to yield maximal compound action potentials(CAPs), as measured at a recording site by another hook electrode 140.

A tripolar platinum/iridium (Pt/Ir) cuff electrode assembly comprisingindividual electrodes 120, 122, and 124 was applied to nerve 150 betweenelectrodes 130 and 140. The electrodes in the cuff were separated bygaps of 1 mm from each other, and the overall length of the cuff was 5mm. (The cuff structure holding electrodes 120, 122, and 124 in place isnot shown.) Current was applied to the electrode assembly through twostimulus isolators coupled to a D/A computer card, and was configuredsuch that electrode 122 served as a cathode, and electrodes 120 and 124served as anodes. A unidirectional action potential was generated bydriving through electrode 122 a total cathodic current of 0.8 mA, andcontrolling electrodes 120 and 124 such that 0.1 mA passed throughelectrode 120, and 0.7 mA passed through electrode 124. The 0.1 mA wasfound to be sufficient to generate an action potential traveling towardselectrodes 130, which collided with and ended propagation of actionpotentials generated by hook electrodes 130. Similarly, the 0.7 mA wasfound to be sufficient to inhibit propagation of action potentials whichwere generated responsive to the operation of the cuff electrodeassembly. In these experiments, the current driven through electrodes120, 122, and 124 was quasi-trapezoidal in time, having a duration of200 microseconds and a decay constant of 300 microseconds.

FIG. 3A shows the results of application of a stimulation pulse throughelectrodes 130, without any blocking applied through the electrodeassembly of electrodes 120, 122, and 124. A complete compound actionpotential, characteristic of this preparation, is seen to peak atapproximately T=2.5 milliseconds. In FIG. 3B, stimulation was appliedthrough electrodes 130 at the same time that electrodes 120, 122, and124 drove blocking currents into nerve 150 as described hereinabove. TheCAP is seen to be very significantly reduced, because the actionpotentials traveling in one direction from electrodes 130 collided withthe “blocking” action potentials propagating in the other direction fromelectrodes 120 and 122. In FIG. 3C, the stimulation through electrodes130 was followed, after a 200 microsecond delay, by the generation ofthe blocking currents through electrodes 120, 122, and 124. In thiscase, it is seen that action potentials propagating through fasterfibers had already passed the cuff electrode assembly by the time thatthe action potentials propagating from electrode 120 had been initiated.Since there was no elimination by collision, the fastest moving actionpotentials leaving electrodes 130 were detected by electrode 140.However, slower action potentials were eliminated, such that the overallCAP area is seen to be significantly smaller in FIG. 3C than in FIG. 3A.

For some applications, this technique is utilized to affect actionpotential propagation in the pelvic nerve, or in another nerve, in orderto treat erectile dysfunction. Preferably, the signals applied areconfigured so as to cause the arterial dilation responsible forerection, e.g., by collision-blocking action potentials propagating insympathetic C fibers which innervate arteries of the penis that, whenconstricted, prevent erection. By inhibiting action potentialpropagation in these fibers, the arteries dilate, and erection isachieved. Preferably, the signal is applied in a unidirectional mode, soas to prevent undesired action potentials from being conveyed to thepenis in response to the applied signal.

Alternatively or additionally, high frequency blocking currents areapplied to sympathetic fibers, e.g., at frequencies above approximately500 Hz, so as to reduce arterial constriction and facilitate erection.Further alternatively or additionally, simple anodal block is applied tothe sympathetic fibers, using techniques known in the art or describedherein, in order to facilitate erection.

In combination with some of these techniques, or separately therefrom,stimulation may be applied to parasympathetic fibers, in order tofacilitate erection. Preferably, the stimulation is applied at a pelvicsite in a unidirectional mode, such that unpleasant or painful signalsare not conveyed to the brain in response to the applied stimulation.Typically, stimulation currents having frequencies in the range of 10-50Hz are applied to the pelvic or pudendal nerves.

In a preferred embodiment, collision blocking or another inhibitoryelectrical signal is applied to parasympathetic fibers in order tosupport ejaculation preferably following a period of erection.Alternatively or additionally, ejaculation is facilitated by electricalstimulation applied to sympathetic fibers.

For some applications, nerve stimulation or inhibition techniquesdescribed herein are used in the treatment of heart failure or in thetreatment of other cardiac pathologies, e.g., arrhythmias such asfibrillation, tachycardia, or bradycardia. By way of analogy to betablockers, which are known to inhibit sympathetic input to the heart andthereby treat tachycardia and heart failure, some embodiments of thepresent invention electrically inhibit the heart's sympathetic input inorder to reduce cardiac contractility and rate. By contrast to betablockers, however, these embodiments of the present invention do nothave the disadvantages associated with pharmaceutical regimes (e.g., aneed to follow a daily pill-taking schedule, as well as possiblesystemic effects of the beta blockers). As a result of these and otherdisadvantages, beta blockers are not suitable for a significant portionof the patient population.

Typically, electrical inhibition as provided by these preferredembodiments of the present invention is applied to sympathetic fibers bymeans of one or more of the following techniques described herein: (a)anodal blocking, (b) high-frequency blocking, preferably applied in aunidirectional mode, or (c) inhibiting action potentials which arecoming from the CNS to the heart, by sending collision-blocking actionpotentials from an electrode implantation site on a nerve, along Cfibers thereof, towards the CNS. This latter technique is alsopreferably applied in a unidirectional mode, so as to minimize actionpotential propagation towards the heart responsive to the appliedsignals. These techniques may be practiced using electrodes implanted onor placed in the vicinity of any one or more sympathetic nervesinnervating the heart, such as, for example, thoracic branches of thesuperior cervical nerve, the middle cervical nerve, or the inferiorcervical nerve.

Alternatively or additionally, parasympathetic stimulation of the heartis enhanced, in order to achieve a result generally similar to that ofbeta blockers. For example, electrodes may be placed on the portion ofthe vagus nerve that innervates the heart, and driven in aunidirectional mode to enhance the parasympathetic signaling regulatingthe heart, substantially without causing undesired action potentials topropagate towards the CNS responsive to the applied stimuli.

Preferably, sympathetic inhibition and/or parasympathetic stimulation asdescribed are applied in response to one or more sensed cardiacparameters or other physiological parameters, such as heart rate,electrocardiogram, blood pressure, or indicators of decreased cardiaccontractility. Alternatively, the stimulation or inhibition is appliedintermittently, constantly, based on the time of day, or in response toa patient input.

For some applications, chronic obstructive pulmonary disease (COPD) istreated by inhibiting parasympathetic stimulation of the lungs, usingany of the techniques described herein, e.g., (a) anodal blocking ofparasympathetic fibers innervating the lungs, (b) high-frequencyblocking of parasympathetic fibers innervating the lungs, preferablyapplied in a unidirectional mode, and/or (c) inhibition ofparasympathetic action potentials coming from the CNS to the lungs, bysending collision-blocking action potentials from an electrodeimplantation site on a nerve, preferably along C fibers thereof, towardsthe CNS. Preferably, this latter technique is practiced in aunidirectional mode, so as to avoid sending additional action potentialstowards the lungs as a result of the applied currents. In addition to orin place of these techniques, sympathetic nerves innervating the lungmay be stimulated, so as to enhance the sympathetic pulmonary responseand treat the COPD. These techniques, applied separately or incombination, are believed to be well-suited for many patientpopulations, e.g., asthmatics, and are preferably configured so as toavoid, replace, or reduce the pharmaceutical regimes which many COPDpatients must follow, such as frequent inhaler use.

In other applications, hyperhidrosis (excess sweating) is treated bysuppressing action potentials from propagating in sympathetic fibersinnervating sweat glands. For example, any of the inhibition techniquesdescribed herein may be adapted for use with electrodes placed on anerve leaving one of the cervicothoracic ganglia towards one of thepatient's arms, in order to facilitate a reduction of perspiration bythe axillary sweat glands. In particular, preferred techniques include:(a) anodal blocking of sympathetic fibers innervating the axillary sweatglands, (b) high-frequency blocking of sympathetic fibers innervatingthe axillary sweat glands, preferably applied in a unidirectional mode,and/or (c) inhibition of sympathetic action potentials coming from thecervicothoracic ganglion to the axillary sweat glands, by sendingcollision-blocking action potentials from an electrode implantation siteon a suitable nerve towards the cervicothoracic ganglia.

In a preferred embodiment, pain is treated by applying a tripolarelectrode array at a peripheral nerve site between a source of chronicpain and the central nervous system (CNS). Preferably, unidirectionalcollision blocking is applied, as described above, so as to eliminatecentrally-propagating pain signals, while substantially not generatingcentrally-propagating action potentials in response to the applicationof current by the tripolar electrode array. Preferably, the collisionblocking is configured so as to block pain signals but not other sensorysignals.

Advantageously, pain signals generally travel through very small fibers,while other sensory information often propagates in larger fibers. Assuch, the tripolar electrode array (e.g., as shown in FIG. 2) ispreferably driven for between 0.1 and 2 milliseconds, typically 0.3milliseconds, and a greater amount of current is driven through theelectrode proximal to the CNS, and less current through the electrodedistal to the CNS. Preferably, the ratio of these two currents isbetween about 3:1 and 15:1. The inventors of the present patentapplication have found that a stimulation protocol such as thisgenerally generates peripherally-directed action potentials in thepain-carrying fibers, which ultimately collide with and destroycentrally-directed pain signals traveling through the same fibers.Further, this protocol minimizes the generation of peripherally-directedaction potentials in the larger fibers, and thus avoidscollision-blocking of non-pain sensory signals traveling through thesefibers.

If the creation rate of collision-blocking action potentials in the painfibers is sufficiently high, e.g., O(40 Hz), then a substantial portionof the pain signals traveling through the nerve will be destroyed. It isspecifically noted that no sensing of upstream pain signals isnecessary, nor is a patient input required. It is also noted thatalthough pain fibers carrying a pain signal often transmit approximately40 action potentials each second, it may be desirable in some instancesto intentionally allow some of the pain signals to pass, in order toguarantee that the patient remains aware of potentially dangerousconditions in her environment.

A side effect of the pain-treatment technique described hereinabove isthat action potentials propagating in non-pain fibers in eitherdirection may be destroyed if the non-pain action potentials are underthe tripolar electrode assembly during the short period in whichunidirectional action potentials are being created. An adverse result ofaggressive pain treatment (e.g., at 40 Hz), therefore, mighttheoretically include partial numbness or weakness. The inventors havedetermined, however, that the use of multiple tripolar electrode arrays,disposed at respective longitudinal sites along a nerve, cansubstantially reduce this potentially adverse effect to the point whereit does not interfere with the patient's activities of daily livingand/or is not even noticed by the patient.

Preferably, the tripolar electrodes at the different sites are driven togenerate unidirectional action potentials in a manner analogous to awave of green traffic lights, whereby if an action potential travelingthrough a non-pain fiber is not eliminated at one of the tripolarelectrodes, then it is unlikely to be eliminated at any other tripolarelectrode. In particular, this method can be optimized to allow actionpotentials having a predetermined range of conduction velocities to passthrough the plurality of tripolar electrodes.

For example, if it is desired to allow most 50 m/s action potentials topass through, unimpeded by the generation of unidirectional actionpotentials, and if a plurality of tripolar electrode arrays are spacedone every 5 centimeters along a nerve, then each tripolar electrodearray is preferably activated 1 millisecond after its neighbor. If, inthis example, five such tripolar electrode arrays are implanted andactivated in a wave, and if it is desired to eliminate pain-conveyingaction potentials 40 times each second, then each individual tripolarelectrode array is only activated 8 times per second. Consequently, therelatively high frequency non-pain action potentials are only blockedapproximately 8 times per second, which is so low compared to the numberof non-pain action potentials which are allowed to pass, that this isnot expected to have any significant clinical repercussions. Conversely,the undesired pain signals are minimized by this treatment.

Preferably, a calibration procedure is invoked in order to set both thetiming of the generation of the wave, and the relative currents appliedto the anodes in each tripolar electrode. Advantageously, the pluralityof tripolar electrodes at their respective sites along the nerve can beused in and of themselves to facilitate the calibration, without theneed for other electrical sensors to be applied to the nerve. That is,the timing and current profiles of one of the tripolar electrodes can bevaried while its effect is recorded by the other tripolar electrodes attheir respective sites.

It has been observed that the human body can lose sensitivity to aconstant stimulation protocol. The above-cited U.S. Pat. No. 4,338,945to Kosugi et al. notes, for example, that randomizing an appliedelectrical stimulation enhances pain relief. Preferred embodiments ofthe present invention utilize methods described in the Kosugi patent,mutatis mutandis, or other stochastic methods, as appropriate, in orderto randomize one or more parameters of the signals applied to nerves,and thereby enhance the efficacy of the treatments. By thus avoidingusing a predetermined signal, the body's desired response can typicallybe elicited for a longer time period.

For some applications, techniques described herein are carried out usingmethods and apparatus described in U.S. patent application Ser. No.09/843,334, filed Apr. 26, 2001, entitled, “Actuation and control oflimbs through motor nerve stimulation,” which is assigned to theassignee of the present patent application and incorporated herein byreference.

It is noted that while some preferred embodiments of the presentinvention utilize a permanently-implanted set of electrodes, configuredto apply currents as described for many years, the scope of the presentinvention includes the use of these techniques in an acute setting,e.g., after cardiac arrest, in order to treat a condition.

It is to be understood that many of the inhibitory techniques describedherein for application to sympathetic or parasympathetic fibers may beapplied in combination with—or may be replaced by—stimulation ofparasympathetic or sympathetic fibers, respectively.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description. For example, specificelectrical treatments are described herein for specific clinicalconditions by way of example, but those of ordinary skill in the artwill understand that the same treatments may be applied to the same orother nerves in the treatments of other conditions. In particular,unless there is a specific clinical counter-indication or othercounter-indication, it is to be understood that the scope of the presentinvention includes applying any of the sensing and signal applicationmodes described herein and/or recited explicitly in the various claims,either: (a) in the treatment of each medical condition cited hereinand/or recited explicitly in the various claims, or (b) in the treatmentof the symptoms or causes of other medical conditions.

1. A method for treating a condition of a subject, comprising: drivinginto longitudinal nervous tissue of the subject a stimulating current ata first longitudinal location which is capable of inducing actionpotentials that propagate in the nervous tissue in a first directionwhich action potentials include slower and faster action potentials; andsuppressing the slower action potentials from propagating in the nervoustissue in the first direction by applying a blocking current at a secondlongitudinal location after a delay following driving the stimulatingcurrent, and timing the delay to allow passage of the faster actionpotentials, while suppressing the slower action potentials, wherein thelongitudinal nervous tissue includes at least one nerve selected fromthe group consisting of: a sympathetic nerve of the subject, and aparasympathetic nerve of the subject.
 2. A method according to claim 1,wherein driving the stimulating and blocking currents comprises drivingthe stimulating and blocking currents into tissue selected from thegroup consisting of: a pudendal nerve of the subject, a cavernous nerveof the subject, a spinal nerve root of the subject, and a cervical nerveof the subject.
 3. A method according to claim 1, wherein driving thestimulating and blocking currents comprises driving stimulating andblocking currents into the parasympathetic nerve of the subject.
 4. Amethod according to claim 3, wherein driving the stimulating andblocking currents comprises driving the stimulating and blockingcurrents into a nerve of the subject that provides parasympatheticinnervation to a heart of the subject.
 5. A method according to claim 1,wherein driving the stimulating and blocking currents comprises drivingthe stimulating and blocking currents into at least one nerve of thesubject selected from the group consisting of: (a) a nerve of thesubject that provides sympathetic innervation to a lung of the subject,and (b) a nerve of the subject that provides parasympathetic innervationto a lung of the subject, and (c) a nerve that modulates hidrosis of thesubject.
 6. A method according to claim 1, wherein driving thestimulating and blocking currents comprises at least one of the groupconsisting of: (a) configuring the currents to be capable of treatingmuscle spasm of the subject, and (b) configuring the currents to becapable of treating vaginismus of the subject.
 7. A method according toclaim 1, wherein driving the stimulating and blocking currents comprisesconfiguring the stimulating and blocking currents to be capable oftreating an aspect of heart failure of the subject.
 8. A methodaccording to claim 1, wherein driving the stimulating and blockingcurrents comprises configuring the stimulating and blocking currents tobe capable of treating an aspect of cardiac arrhythmia of the subject.9. A method according to claim 1, wherein driving the stimulating andblocking currents comprises configuring the stimulating and blockingcurrents to be capable of treating tachycardia of the subject.
 10. Amethod according to claim 1, wherein driving the stimulating andblocking currents comprises configuring the stimulating and blockingcurrents to be capable of treating bradycardia of the subject.
 11. Amethod according to claim 1, wherein driving the stimulating andblocking currents comprises configuring the stimulating and blockingcurrents to be capable of treating an aspect of chronic obstructivepulmonary disorder (COPD) of the subject.
 12. A method according toclaim 1, and comprising implanting electrodes in a vicinity of thenervous tissue, wherein driving the stimulating and blocking currentscomprises driving the stimulating and blocking currents through theelectrodes on a chronic basis.
 13. A method according to claim 1, andcomprising placing electrodes in a vicinity of the nervous tissue inresponse to an acute occurrence, wherein driving the stimulating andblocking currents comprises driving the stimulating and blockingcurrents through the electrodes, and wherein the method comprisesremoving the electrodes following the acute occurrence.
 14. A methodaccording to claim 1, wherein driving the stimulating and blockingcurrents comprises configuring the stimulating and blocking currents soas to induce action potential propagation primarily in A fibers of thenervous tissue.
 15. A method according to claim 1, wherein driving thestimulating and blocking currents comprises driving the stimulating andblocking currents into the sympathetic nerve of the subject.
 16. Amethod according to claim 15, wherein driving the stimulating andblocking currents comprises driving the stimulating and blockingcurrents into a nerve of the subject that provides sympatheticinnervation to a heart of the subject.
 17. A method according to claim1, wherein suppressing the slower action potentials comprisesconfiguring the blocking current to eliminate, by collision blocking,the slower action potentials propagating in the second direction.
 18. Amethod according to claim 1, wherein the delay has a duration of 200microseconds.